Micro integrated cardiac pacemaker and distributed cardiac pacing system

ABSTRACT

A micro integrated cardiac pacemaker includes a control unit for outputting a control signal according to cardiograph information, heart stimulating means for stimulating heart tissue in response to the control signal, cardiograph information extracting means for extracting cardiograph information and outputting it to the control unit, and a power supply unit for supplying drive power. The power supply unit is a biological fuel cell that takes out electrons by oxidation of a biological fuel. The biological fuel cell includes an anode and a cathode. An oxidase of a biological fuel and a mediator are immobilized on the cathode. Blood and/or body fluid are used as an electrolytic solution, and a biological fuel and oxygen in the blood and/or the fluid are used. The biological fuel cell is attached to the end of a catheter and implanted into the heart, and the catheter is withdrawn, without incising the breast.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention concerns an ultra miniature integrated cardiacpacemaker and distributed cardiac pacing system. The invention providesan ultra miniature integrated cardiac pacemaker and distributed cardiacpacing system that allows pacing of the heart without the need forconventional lead wires that connect the electrodes and the main body ofthe pacemaker, and allows implantation by catheter manipulation withoutincising the chest wall, which avoids imposing an extra burden on theuser.

In this invention, “ultra miniature” refers to the minute size of thepacemaker to the extent that it can be attached to the tip of acatheter.

2. Description of Related Art

A cardiac pacemaker is a device that controls the rhythm of the heart bydelivering electrical impulses to the heart, and is indicated for use inpatients with symptoms of bradyarrhythmia.

A conventional cardiac pacemaker includes the main body of the cardiacpacemaker (generator), lead wires, and electrodes that transmit astimulating pulse to the myocardium. The main body of the cardiacpacemaker and the electrodes are connected by lead wires. However,conventional pacemakers have the following problems.

Since the main body of the cardiac pacemaker and the electrodes areconnected by lead wires, cases of breaking of the lead wires haveoccurred. Breakage of the lead wires results in defective pacing. Inaddition, there have been also cases of venous obstruction by the leadwires.

Moreover, during the early stages after implantation of the cardiacpacemaker, a shift in position of the electrodes may cause defectivepacing. When a shift in position of the electrodes occurs, a secondoperation has to be performed, which adds extra strain for the patient.

Furthermore, if there is a defective hermetic sealing structure at thejunction between the cardiac pacemaker main body and the lead wires,this may lead to defective pacemaker movement. Problems with electricalsafety have also occurred.

In the Unexamined Japanese Patent Publication Heisei No. 5-245215, acardiac pacemaker is described in which the signals for cardiacstimulation are delivered from the cardiac pacemaker main body to thestimulation electrodes by wireless transmission, thus eliminating thelead wires between the cardiac pacemaker main body and the electrodes.

However, even for this type of cardiac pacemaker, surgical implantationof the pacemaker cannot be avoided, and there have been cases in whichskin necrosis occurred at the cardiac pacemaker implantation site.

Also, in the above-mentioned cardiac pacemaker, although wirelesscommunication is conducted between the pacemaker main body and theelectrodes, there is no communication between the electrodes. Synchronybetween the multiple electrodes being used is controlled by thepacemaker main body.

The present invention was developed in order to solve the aboveproblems, and to provide an ultra miniature integrated cardiac pacemakerand distributed cardiac pacing system with the following features: thegenerator function of electric stimulus by the pacemaker main body isintegrated with the electrodes, thus allowing pacing of the heartwithout the need for conventional lead wires connecting the electrodesand pacemaker main body. By integrating the control unit of thepacemaker main body and the electrodes, there is no need to implant thepacemaker main body, which avoids imposing an extra burden on the user.

SUMMARY OF THE INVENTION

The ultra miniature integrated cardiac pacemaker of the presentinvention requires no chest incision, and is implanted in the heart byattaching it to the tip of a catheter and extracting the catheter afterimplanting.

In one embodiment, the pacemaker includes a control unit that outputscontrol signals, a heart stimulating means that responds to the controlsignal and electrically stimulates the heart tissue, anelectrocardiographic information detecting means that detects theelectrocardiographic information and outputs it to the control unit, anda power unit that supplies the driving power.

The control unit outputs the control signals based onelectrocardiographic information.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as an electrolyte solution and utilizes biologicalfuels and oxygen in blood and/or body fluid.

In another embodiment of the present invention, an ultra miniatureintegrated cardiac pacemaker includes a control unit that outputscontrol signals, a heart stimulating means that responds to the controlsignal and electrically stimulates the heart tissue, anelectrocardiographic information detecting means that detects theelectrocardiographic information and outputs it to the control unit, atransmitting means that modulates the electrocardiographic informationand control signals to be sent outside, and a power unit that suppliesthe driving power.

The control unit outputs the control signals based onelectrocardiographic information.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as an electrolyte solution and utilizes biologicalfuels and oxygen in blood and/or body fluid.

In a third embodiment, an ultra miniature integrated cardiac pacemakerincludes a control unit that outputs control signals, a heartstimulating means that responds to the control signal and electricallystimulates the heart tissue, an electrocardiographic informationdetecting means that detects the electrocardiographic information andoutputs it to the control unit, a receiving means that receives anddemodulates the information sent from outside, and a power unit thatsupplies the driving power. It is designed such that the informationsent from outside is input into the control unit.

The control unit outputs control signals based on information sent fromoutside and/or electrocardiographic information.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as an electrolyte solution and utilizes biologicalfuels and oxygen in blood and/or body fluid.

In yet another embodiment, an ultra miniature integrated cardiacpacemaker includes a control unit that outputs control signals, a heartstimulating means that responds to the control signal and electricallystimulates the heart tissue, an electrocardiographic informationdetecting means that detects the electrocardiographic information andoutputs it to the control unit, a transmitting means that modulates theelectrocardiographic information and control signals to be sent outside,a receiving means that receives and demodulates the information sentfrom outside, and a power unit that supplies the driving current. It isdesigned such that the information sent from outside is input into thecontrol unit.

The control unit outputs control signals based on information sent fromoutside and/or electrocardiographic information.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as electrolyte solution and utilizes biological fuelsand oxygen in blood and/or body fluid.

Another embodiment discloses a cardiac pacing system including an ultraminiature integrated cardiac pacemaker placed in the atrial myocardium.

The ultra miniature integrated cardiac pacemaker is equipped with acontrol unit that outputs control signals, a power unit that suppliesthe driving power, a heart stimulating means that responds to thecontrol signals and electrically stimulates the atrial myocardium, andan electrocardiographic information detecting means that detects theelectrocardiographic information including at least intracardiac P waveinformation.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as an electrolyte solution and utilizes biologicalfuels and oxygen in blood and/or body fluid.

The control unit is equipped with a stimulation timing determining meansthat decides the timing of stimulation to generate control signals, anda stimulation timing changing means that changes the timing ofstimulation to generate control signals. It is characterized by theability to change the timing of stimulation to generate the controlsignal, in case intracardiac P wave information is detected within apreset time interval.

Yet another embodiment concerns a distributed cardiac pacing systemincluding an electrocardiographic information detecting device placed inthe atrial myocardium and an ultra miniature integrated cardiacpacemaker placed in the ventricular myocardium.

The electrocardiographic information detecting device is equipped withan electrocardiographic information detecting means that detects theelectrocardiographic information including at least intracardiac P waveinformation, a transmitting means that modulates theelectrocardiographic information detected and sends the information tothe ultra miniature integrated cardiac pacemaker, and a power unit thatsupplies the driving current.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as an electrolyte solution and utilizes biologicalfuels and oxygen in blood and/or body fluid.

The ultra miniature integrated cardiac pacemaker is equipped with areceiving means that receives and demodulates the electrocardiographicinformation sent from the electrocardiographic information detectiondevice, a control unit that outputs control signals, a power unit thatsupplies the driving power, and a heart stimulating means that respondsto the control signal and electrically stimulates the ventricularmyocardium.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as an electrolyte solution and utilizes biologicalfuels and oxygen in blood and/or body fluid.

The control unit is equipped with a stimulation timing determining meansthat decides the timing of stimulation to generate the control signals,and a stimulation timing changing means that changes the timing ofstimulation to generate the control signals.

It is characterized by a mechanism to generate control signals whenintracardiac QRS complex information is not detected within a given timeafter the detection of intracardiac P wave, and suppress the controlsignals when QRS complex information is detected within a given timeafter the detection of intracardiac P wave information.

Another embodiment discloses a distributed cardiac pacing systemincluding a first ultra miniature integrated cardiac pacemaker placed inthe atrial myocardium and a second ultra miniature integrated cardiacpacemaker placed in the ventricular myocardium.

The first ultra miniature integrated cardiac pacemaker is equipped witha control unit that outputs control signals, a power unit that suppliesthe driving power, a heart stimulating means that responds to thecontrol signal and electrically stimulates the atrial myocardium, anelectrocardiographic information detecting means that detects theelectrocardiographic information including at least intracardiac P waveinformation, a transmitting means that modulates theelectrocardiographic information and sends the information to the secondultra miniature integrated cardiac pacemaker, and a receiving means thatreceives and demodulates the electrocardiographic information sent fromthe second ultra miniature integrated cardiac pacemaker.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as an electrolyte solution and utilizes biologicalfuels and oxygen in blood and/or body fluid.

The electrocardiographic information sent from the second ultraminiature integrated cardiac pacemaker is input into the control unit;and the control unit is equipped with a stimulation timing determiningmeans that decides the timing of stimulation to generate the controlsignals, and a stimulation timing changing means that changes the timingof stimulation to generate the control signals.

The second ultra miniature integrated cardiac pacemaker is equipped witha control unit that outputs control signals, a power unit that suppliesthe driving power, a heart stimulating means that responds to thecontrol signal and electrically stimulates the ventricular myocardium,an electrocardiographic information detecting means that detects theelectrocardiographic information including at least intracardiac QRScomplex information, a transmitting means that modulates theelectrocardiographic information and sends the information to the firstultra miniature integrated cardiac pacemaker, and a receiving means thatreceives and demodulates the electrocardiographic information sent bythe first ultra miniature integrated cardiac pacemaker.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as electrolyte solution and utilizes biological fuelsand oxygen in blood and/or body fluid.

The electrocardiographic information sent from the first ultra miniatureintegrated cardiac pacemaker is input into the control unit; and thecontrol unit is equipped with a stimulation timing determining meansthat decides the timing of stimulation to generate the control signal,and a stimulation timing changing means that changes the timing ofstimulation to generate the control signal.

The control unit of the first ultra miniature integrated cardiacpacemaker generates the control signal when intracardiac P waveinformation is not detected within a given time interval, and suppressesthe generation of control signals when intracardiac P wave informationis detected within a given time.

The control unit of the second ultra miniature integrated cardiacpacemaker generates control signals when intracardiac QRS complexinformation is not detected within a given time after detection ofintracardiac P wave information, and suppresses the generation ofcontrol signals when intracardiac QRS complex information is detectedwithin a given time after detection of intracardiac P wave information.

The system is also characterized by the following mechanism: if thesecond ultra miniature integrated cardiac pacemaker detects intracardiacQRS complex information due to spontaneous ventricular contraction, thecontrol unit of the first ultra miniature integrated cardiac pacemakersuppresses the detection of intracardiac P wave information for a giventime interval.

Another embodiment discloses a distributed cardiac pacing systemincluding an electrocardiographic information detection device placed inthe atrial myocardium and multiple ultra miniature integrated cardiacpacemakers placed in the ventricular myocardium.

The electrocardiographic information detection device is equipped withan electrocardiographic information detecting means that detects theelectrocardiographic information including at least intracardiac P waveinformation, a transmitting means that modulates the detectedelectrocardiographic information and sends the information to the ultraminiature integrated cardiac pacemakers, and a power unit that suppliesthe driving power.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as electrolyte solution and utilizes biological fuelsand oxygen in blood and/or body fluid.

The ultra miniature integrated cardiac pacemakers are equipped with acontrol unit that outputs control signals, a power unit that suppliesthe driving power, a heart stimulating means that responds to thecontrol signals and electrically stimulates the ventricular muscle, anelectrocardiographic information detecting means that detects theelectrocardiographic information including at least intracardiac QRScomplex information, a transmitting means that modulates theelectrocardiographic information and sends the information to otherultra miniature integrated cardiac pacemakers, and a receiving meansthat receives and demodulates the electrocardiographic information sentfrom other ultra miniature integrated cardiac pacemakers.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as an electrolyte solution and utilizes biologicalfuels and oxygen in blood and/or body fluid.

The electrocardiographic information sent from other ultra miniatureintegrated cardiac pacemakers is input into the control unit; and thecontrol unit is equipped with a stimulation timing determining meansthat decides the timing of stimulation to generate the control signals,and a stimulation timing changing means that changes the timing ofstimulation to generate the control signals.

The system is characterized by the following mechanism: when individualultra miniature integrated cardiac pacemakers do not detect intracardiacQRS complex information within the respective preset times afterdetection of intracardiac P wave information, the control units of theultra miniature integrated cardiac pacemakers generate control signals;whereas when QRS complex information is detected within given timeintervals after detection of intracardiac P wave information, thecontrol units generate control signals synchronous to the earliesttiming at which the intracardiac QRS complex information is firstdetected.

Yet another embodiment discloses a distributed cardiac pacing systemincluding a first ultra miniature integrated cardiac pacemaker placed inthe atrial myocardium and multiple second ultra miniature integratedcardiac pacemakers placed in the ventricular myocardium.

The first ultra miniature integrated cardiac pacemaker is equipped witha control unit that outputs control signals, a power unit that suppliesthe driving power, a heart stimulating means that responds to thecontrol signals and electrically stimulates the atrial myocardium, anelectrocardiographic information detecting means that detects theelectrocardiographic information including at least intracardiac P waveinformation, a transmitting means that modulates theelectrocardiographic information and sends the information to multiplesecond ultra miniature cardiac pacemakers, and a receiving means thatreceives and demodulates the electrocardiographic information sent bythe multiple second ultra miniature integrated cardiac pacemakers.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as electrolyte solution and utilizes biological fuelsand oxygen in blood and/or body fluid.

The electrocardiographic information sent from the multiple second ultraminiature integrated cardiac pacemakers are input into the control unit;and the control unit is equipped with a stimulation timing determiningmeans that decides the timing of stimulation to generate the controlsignals, and a stimulation timing changing means that changes the timingof stimulation to generate the control signals.

The multiple second ultra miniature integrated cardiac pacemakers areeach equipped with a control unit that outputs control signals, a powerunit that supplies the driving current, a heart stimulating means thatresponds to the control signal and electrically stimulates theventricular myocardium, an electrocardiographic information detectingmeans that detects the electrocardiographic information including atleast intracardiac QRS complexes, a transmitting means that modulatesthe electrocardiographic information and sends the information to thefirst and other second ultra miniature cardiac pacemakers, and areceiving means that receives and demodulates the electrocardiographicinformation sent from the first and other second ultra miniatureintegrated cardiac pacemakers.

The power unit is preferably a biological fuel cell that extractselectrons from oxidative reactions of biological fuels. The biologicalfuel cell is composed of an anode electrode and a cathode electrode. Theanode electrode is coated with immobilized oxidative enzymes forbiological fuels and mediators. The biological fuel cell uses bloodand/or body fluid as an electrolyte solution and utilizes biologicalfuels and oxygen in blood and/or body fluid.

The electrocardiographic information sent from the first and othersecond ultra miniature integrated cardiac pacemakers is input into thecontrol unit; and the control unit is equipped with a stimulation timingdetermining means that decides the timing of stimulation to generate thecontrol signals, and a stimulation timing changing means that changesthe timing of stimulation to generate the control signals.

The control unit of the first ultra miniature integrated cardiacpacemaker generates control signals when intracardiac P wave informationis not detected within a given time interval, and suppresses thegeneration of control signal when intracardiac P wave information isdetected within a given time.

The control units of the second ultra miniature integrated cardiacpacemakers generate control signals when intracardiac QRS complexinformation is not detected by individual ultra miniature integratedcardiac pacemakers within the respective preset time intervals after thedetection of intracardiac P wave information; whereas if intracardiacQRS complex information is detected within the given time intervalsafter the detection of intracardiac P wave information, the controlunits generate control signals synchronous to the earliest timing atwhich intracardiac QRS complex information is detected.

The system is also characterized by the following mechanism: when one ofthe multiple second ultra miniature integrated cardiac pacemakersdetects intracardiac QRS complex information due to spontaneousventricular contraction, the control unit of the first ultra miniatureintegrated cardiac pacemaker suppresses the detection of intracardiac Pwave information for a given interval.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a simplified block diagram of an ultra miniature integratedcardiac pacemaker in accordance with the first embodiment.

FIG. 2 is a simplified block diagram of an ultra miniature integratedcardiac pacemaker in accordance with the first embodiment.

FIG. 3 is a simplified block diagram of an ultra miniature integratedcardiac pacemaker in accordance with the second embodiment.

FIG. 4 is a simplified block diagram of an ultra miniature integratedcardiac pacemaker in accordance with the third embodiment.

FIG. 5 is a simplified block diagram of an ultra miniature integratedcardiac pacemaker in accordance with the fourth embodiment.

FIG. 6 is a schematic diagram illustrating a first application of theultra miniature integrated cardiac pacemaker in accordance with thepresent invention (the first distributed cardiac pacing system).

FIG. 7 is a schematic diagram illustrating a second application of theultra miniature integrated cardiac pacemaker in accordance with thepresent invention (the second distributed cardiac pacing system).

FIG. 8 is a block diagram illustrating an outline of theelectrocardiographic information detection device.

FIG. 9 is a schematic diagram illustrating a third application of theultra miniature integrated cardiac pacemaker in accordance with thepresent invention (the third distributed cardiac pacing system).

FIG. 10 is a schematic diagram illustrating a fourth application of theultra miniature integrated cardiac pacemaker in accordance with thepresent invention (the fourth distributed cardiac pacing system).

DETAILED DESCRIPTION OF THE INVENTION

The present invention is described in detail below while referring tothe figures. FIG. 1 is a simplified block diagram of an ultra miniatureintegrated cardiac pacemaker (100) in accordance with a first embodimentof this invention.

The ultra miniature integrated cardiac pacemaker (100) in thisembodiment is composed of a control unit (2) that outputs controlsignals, a heart stimulating means (3) that responds to the controlsignals and electrically stimulates the heart tissue, anelectrocardiographic information detecting means (5) that detects theelectrocardiographic information and outputs it to the control unit (2),a transmitting means (10) that modulates the control signals output fromthe control unit (2) and/or electrocardiographic information detected bythe electrocardiographic information detecting means (5) and sends theinformation outside, a receiving means (9) that receives and demodulatesthe information sent from outside, and a power unit (4) that suppliesthe driving current.

The heart stimulating means (3) responds to the control signal outputfrom the control unit (2) and electrically stimulates the heart tissue.The heart stimulating means (3) as shown in the diagram is able tostimulate the heart tissue. The heart stimulating means (3) includes astimulating unit (31) that responds to the control signals output fromthe control unit (2) and outputs heart stimulating pulses to stimulatethe heart tissue, and two heart stimulating electrodes (32) thatstimulate the heart tissue in response to the output pulses.

The electrocardiographic information detecting means (5) detects theelectrocardiographic information at the site where the ultra miniatureintegrated cardiac pacemaker is placed. The detectedelectrocardiographic information is output to the control unit (2). Theelectrocardiographic information detected by the electrocardiographicinformation detecting means (5) includes P wave information, QRS complexinformation, T wave information, or Q-T time, A-H time, H-V time (whereA is atrial potential, H is His bundle potential, and V is ventricularpotential).

The electrocardiographic information detecting means (5) as shown in thediagram is composed of two electrocardiographic information recordingelectrodes (53) that detect the applied site electrocardiographicinformation at the placement site, an amplifying unit (51) thatamplifies the electrocardiogram, and an A/D conversion (52) unit thatconverts the detected electrocardiographic information into digitalsignals. The electrocardiographic information detecting means (5) isdesigned such that the converted electrocardiographic information isoutput to the control unit (2).

The transmitting means (10) is composed of a modulating unit (11) thatinputs and modulates the control signals output from the control unit(2) and/or electrocardiographic information, and a transmitting unit(12) that sends the modulated control signals to the outside via carrierwaves; by which the modulated control signals are sent to the outside(such as to other ultra miniature integrated cardiac pacemakers, notshown in the diagram).

By transmitting control signals and electrocardiographic information viacarrier waves to outside sites such as other cardiac pacemakers, it ispossible, for example, to activate two or more cardiac pacemakerssynchronously. Moreover, since carrier waves are used for transmission,there is no need for lead wires, and this method avoids imposing anextra burden on the user.

The receiving means (9) is composed of a receiving unit (91) thatreceives information transmitted from the outside via carrier waves, anda demodulating unit (92) that demodulates the information received. Itis designed such that the demodulated information is input into thecontrol unit (2). Based on this information and/or electrocardiographicinformation, control signals are generated in the control unit (2) andoutput to the heart stimulating means (3).

The information transmitted from the outside includeselectrocardiographic information and control signals sent from othercardiac pacemakers.

By equipping the receiving means (9) that receives information from, forinstance, other cardiac pacemakers, it is possible to activate thecardiac pacemaker synchronously with other cardiac pacemakers. Moreover,since there is no need for lead wires, this method avoids imposing extraburden on the user.

Possible modes of communication between pacemakers executed by thetransmitting means (10) and receiving means (9) include, but are notlimited to, spread spectrum communication using radio waves orultrasound waves, and ultra wide band communication. There is norestriction on the mode of communication. Any method can be used as longas it provides reliable communication between pacemakers.

The power unit (4) is designed to supply a power source necessary todrive the ultra miniature integrated cardiac pacemaker. As a power unit(4), in general, it is possible to use a lithium battery or fuel cells.However, in the conventional cardiac pacemakers, the power unit thatsupplies the electrical source is the largest component. Toultra-miniaturize the cardiac pacemaker, it is necessary to miniaturizethe power unit. For the ultra miniature integrated cardiac pacemaker(100) according to the present invention, a biological fuel cell ispreferably used as the power unit (4).

If a biological fuel cell is used as the power unit, biological fuelssuch as glucose and oxygen, which are necessary to drive the biologicalfuel cell, are available in constant supply inside the body. The volumeof the power unit (4) depends only on the size of the electrodes, makingit possible to miniaturize the volume of the power unit (4). Moreover,metabolites and intermediate metabolic products of sugars (e.g.,glucose), such as water, carbon dioxide and gluconolactone, are safe forthe human body and they are rapidly removed from the vicinity of theelectrodes by blood flow. Biological fuel cells that use enzymes ascatalysts can operate under mild conditions such as neutral pH and roomtemperature.

One example of a biological fuel cell used in this invention is thewell-known conventional biological fuel cell that extracts electronsfrom oxidative reactions of biological fuels. This biological fuel celluses sugars (such as glucose) and oxygen, both supplied by the body, asfuels, and utilizes enzymes as biological catalysts.

An example of the composition of the preferable biological fuel cell(40) for this invention will be explained by referring to the diagram.FIG. 2 is a schematic diagram illustrating the simplified structure ofthe biological fuel cell (40) as the power unit in the ultra miniatureintegrated cardiac pacemaker (100) of the first embodiment.

The biological fuel cell (40) is composed of an anode (41) and a cathode(42). This biological fuel cell utilizes blood or body fluid as theelectrolyte solution, and also utilizes sugars and oxygen in blood andbody fluid as biological fuels. Therefore, the anode electrode (41 a)and the cathode electrode (42 a) are positioned so as to be in contactwith blood or body fluid. In FIG. 2, the anode electrode (41 a) and thecathode electrode (42 a) are designed to be in contact with blood, andthe heart stimulating electrode (32) and the electrocardiographicinformation recording electrode (53) are in contact with the myocardialtissue.

The anode (41) is composed of an anode electrode (41 a) and an immobilelayer (41 b) coating the surface of the anode electrode (41 a). A goldelectrode, etc. is preferably used as the anode electrode (41 a).

Oxidative enzymes of biological fuels and mediators necessary for theoxidation of biological fuels are immobilized on the surface of theanode electrode (41 a).

Carbohydrates are used as biological fuels. Examples of carbohydratesare monosaccharides such as glucose and fructose, disaccharides such asmannitol and sucrose, and pentoses such as xylose and arabinose.Glucose, which can be supplied easily by the body, is preferably used asthe fuel.

Any oxidative enzymes that oxidize biological fuels can be used in thepresent invention. For example, enzymes called oxidases and hydrogenasescould be used. If glucose is used as the biological fuel, glucoseoxidase and glucose dehydrogenase can be used. Glucose dehydrogenase ispreferable.

Any mediator that can transfer electrons released from the biologicalfuel to the anode electrode (41 a) can be used in the present invention.Some examples include, but are not limited to, the so-called coenzymessuch as flavin adenine dinucleotide phosphate, enzymes such as laccase,quinines such as pyrrolo-quinoline quinine, and osmium complex, as wellas their combinations.

The oxidative enzymes and mediators are immobilized on the surface ofthe anode electrode (41 a) to form an immobile layer (41 b). There is norestriction on the method of immobilization, and any method well knownto immobilize enzymes onto an electrode surface can be used. Forexample, a gold disc electrode can be used as the substrate, andaminoethane-thiol is adsorbed on the surface of the gold electrode toform a monomolecular film followed by modification of the amino groups.After that, the method mixes the oxidative enzyme for biological fuel,the mediator and albumin in a beaker. Then glutaraldehyde is added toallow the enzymes and mediators to cross-link with glutaraldehyde andthen the mixture is applied to the surface of the gold disc electrode.

To ensure that the reaction takes place efficiently at the anode, theimmobile layer (41 b) should preferably be designed such that the anodeelectrode (41 a) does not come into contact with oxygen present in thebody.

The cathode (42) is composed of a cathode electrode (42 a). An exampleof the cathode electrode (42 a) is a platinum electrode. A catalyst toenhance a reaction involving reduction of oxygen is required on thecathode electrode (42 a). The platinum itself can function as thecatalyst.

To ensure that the reaction takes place efficiently at the cathode, itis desirable to form a coating (42 b) on the surface of the cathodeelectrode, which will prevent permeation of substances other than oxygenthat react with the cathode electrode (42 a), and at the same time allowpermeation of oxygen and hydrogen ions.

The biological fuel cell (40) does not have a container filled withelectrolyte solution. Instead, the cathode electrode (41 a) and theanode electrode (42 a) are in contact with the blood or body fluid ofthe body. The blood and body fluid act as the electrolyte solution. Inthe electrolyte solution, biological fuel and oxygen are constantlysupplied by the blood flow, and at the same time metabolic products aredissolved in blood and removed by the blood flow. The supply ofbiological fuel and oxygen as well as the removal of metabolic productsare maintained constant through the mechanism of homeostasis.

Next, the action of the biological fuel cell (40) will be discussed.

Biological fuel is dissolved in blood and body fluid and supplied to theanode (41) surface. The biological fuel supplied to the anode (41)surface is oxidized by the action of the biological fuel oxidativeenzyme immobilized in the immobile layer (41 b), producing carbondioxide, hydrogen ion and intermediate metabolites, as well aselectrons. Carbon dioxide, hydrogen ion and intermediate metabolites aredissolved in blood or body fluid to be excreted. Electrons aretransferred to the anode electrode (41 a) via mediators.

The cathode (42) surface is supplied with oxygen and hydrogen ionsdissolved in blood and body fluid, and these ions react in the presenceof electrons transmitted from the anode electrode (41 a) to the cathodeelectrode (42 a), and form water. This reaction generates an electriccurrent, which is used as the driving power source.

Based on the program already saved in the memory (7) as well as onelectrocardiographic information output from the electrocardiographicinformation detecting means (5) and information transmitted from theexterior, the control unit (2) generates control signals and outputs thesignals into the heart stimulating means (3).

For instance, the control unit (2) is equipped with a stimulation timingdetermining means that decides the timing of stimulation to generatecontrol signals, and a stimulation timing changing means that changesthe timing of stimulation to generate control signals. Usually this unitis programmed to generate control signals at stimulation timing at apredetermined frequency. It is also programmed to change the stimulationtiming when certain conditions are fulfilled; for instance, in caseintracardiac P wave information is detected within a given timeinterval.

Furthermore, this invention can be equipped with a communication means(6). The communication means (6) communicates with an externalprogrammer (8) installed external to the ultra miniature integratedcardiac pacemaker, and is used to change the pacing program saved in thememory (7). By this means, even after implantation of the ultraminiature integrated cardiac pacemaker in the patient, it is possible touse the external programmer (8) to change the pacing program saved inthe memory (7) as appropriate for the particular patient.

For communication between the external programmer (8) and communicationmeans (6) when a patient is implanted with multiple ultra miniatureintegrated cardiac pacemakers, by setting different frequencies for theindividual ultra miniature integrated cardiac pacemakers, for example,it is possible to change the pacing program for each ultra miniatureintegrated cardiac pacemaker. Also, by conducting spread spectrumcommunication or by giving each pacemaker an ID, it is possible tochange the pacing program of each ultra miniature integrated cardiacpacemaker.

Next, the ultra miniature integrated cardiac pacemaker of the secondembodiment (110) of the present invention will be explained. Thedifference between the ultra miniature integrated cardiac pacemaker inthe second embodiment (110) and the aforementioned ultra miniatureintegrated cardiac pacemaker of the first embodiment (100) is that theformer has no transmitting means (10) or receiving means (9).

The ultra miniature integrated cardiac pacemaker of the secondembodiment (110) can be used when there is no need to synchronizemovements with other cardiac pacemakers.

Based on the control program already saved in the memory (7) and onelectrocardiographic information output from the electrocardiographicinformation detecting means (5), the control unit (2) generates controlsignals and outputs the signals to the heart stimulating means (3).

The other components are the same as those in the aforementioned ultraminiature integrated cardiac pacemaker of the first embodiment (100),therefore explanations are omitted. In FIG. 3, the same numbers areassigned to components identical to those in the first embodiment (100)as shown in FIG. 1.

Next, the ultra miniature integrated cardiac pacemaker of the thirdembodiment (120) of this invention will be explained. FIG. 4 is asimplified block diagram of the ultra miniature integrated cardiacpacemaker in this embodiment (120). The difference between the ultraminiature integrated cardiac pacemaker in this embodiment (120) and theaforementioned ultra miniature integrated cardiac pacemaker of the firstembodiment is that the former has no receiving means (9).

By sending the control signals to the exterior (such as other cardiacpacemakers) via carrier waves, the ultra miniature integrated cardiacpacemaker (120) is able to synchronize and operate with, for instance,one or more other cardiac pacemakers.

Based on the control program already saved in the memory (7) andelectrocardiographic information output from the electrocardiographicinformation detecting means (5), the control unit (2) generates controlsignals and outputs the signals to the heart stimulating means (3).

The other components are the same as those in the aforementioned ultraminiature integrated cardiac pacemaker of the first embodiment,therefore explanations are omitted. In FIG. 4, the same numbers areassigned to components identical to those in the ultra miniatureintegrated cardiac pacemaker in accordance with the first and secondembodiments shown in FIGS. 1 and 3.

Next, the ultra miniature integrated cardiac pacemaker of the fourthembodiment (130) of this invention will be explained. The differencebetween the ultra miniature integrated cardiac pacemaker in thisembodiment (130) and the aforementioned ultra miniature integratedcardiac pacemaker in the first embodiment is that the former has notransmitting means (10) to send control signals and/orelectrocardiographic information to the exterior.

Through the receiving means (9) that receives information from theexterior, for example, from other cardiac pacemakers, the ultraminiature integrated cardiac pacemaker (130) is able to synchronize andoperate with other cardiac pacemakers.

Based on the control program already saved in the memory (7), as well aselectrocardiographic information output from the electrocardiographicinformation detecting means (5) and information transmitted from theexterior, the control unit (2) generates control signals and outputs thesignals to the heart stimulating means (3).

The other components are the same as those in the aforementioned ultraminiature integrated cardiac pacemaker of the first embodiment,therefore explanations are omitted. In FIG. 5, the same numbers areassigned to components identical to those in the ultra miniatureintegrated cardiac pacemakers in accordance with the first threeembodiments shown in FIGS. 1, 3 and 4.

In the ultra miniature integrated cardiac pacemakers of the first fourembodiments, the electrocardiographic information recording electrodes(53) and the heart stimulating electrode (32) are shown as separatecomponents. In reality, the electrocardiographic information recordingelectrode (53) and the heart stimulating electrode (32) may be shared.

Moreover, the receiving unit (91) and the transmitting unit (12) areshown as separate components; however, the receiving unit (91) and thetransmitting unit (12) may also be shared.

Furthermore, by installing in the patient a sensor that measures bodytemperature and blood pressure and outputting the biological informationobtained from these sensors to the control unit (2) of the ultraminiature integrated cardiac pacemakers of the first four embodiments,the control unit (2) is able to generate control signals based on thebiological data.

In addition, for the ultra miniature integrated cardiac pacemakers ofthe first four embodiments, there is no particular restriction on themethod of implanting the pacemaker in the heart and conventional methodsfor catheterization may be adopted. For instance, implantation may bedone by attaching the ultra miniature integrated cardiac pacemaker tothe tip of a catheter and inserting it into the predetermined positioninside the heart, and then withdrawing only the catheter after fixingthe pacemaker in the endocardium. In the ultra miniature integratedcardiac pacemakers of the invention, the generator main body and theelectrodes are integrated, thus obviating the need for lead wires.Therefore, the ultra miniature integrated cardiac pacemakers of theinvention can be made of a size of only 2 to 3 mm in diameter. There isno need to make a wide incision in the chest wall to implant thegenerator main body.

Next, a cardiac pacing system according to this invention using theaforementioned ultra miniature integrated cardiac pacemakers inaccordance with the first four embodiments of this invention will bedescribed while referring to the diagrams.

FIG. 6 is a schematic diagram illustrating the outline of one embodimentof the cardiac pacing system. One ultra miniature integrated cardiacpacemaker (111) is implanted into the atrial endocardium of the patient.In FIG. 6 as well as in FIGS. 7 to 10 to be described below, H indicatesthe heart.

The cardiac pacing system in this embodiment is preferred in cases wherethe atrium has lost the ability to keep pace although the electricalactivity in the atrium and the electrical activity in the ventricleremain synchronized. For example, it may be indicated for patients withsick sinus syndrome in whom only sinus node function is impaired, whileintra-atrial conduction and atrio-ventricular conduction are preserved.

The ultra miniature integrated cardiac pacemaker (111) implanted in theatrium is equipped with a control unit that outputs control signals, aheart stimulating means that responds to the control signals andelectrically stimulates the atrial muscle, and an electrocardiographicinformation detecting means that detects the electrocardiographicinformation including at least intracardiac P wave information. It isdesigned such that the detected electrocardiographic information isoutput into the control unit. In other words, although the ultraminiature integrated cardiac pacemaker of the second embodiment of thisinvention is preferably used, the ultra miniature integrated cardiacpacemaker in accordance with the first, third and fourth embodiments canalso be used as long as they possess the above-mentioned designs.

Also, the control unit is equipped with a stimulation timing determiningmeans that decides the timing of stimulation to generate controlsignals, and a stimulation timing changing means that changes the timingof stimulation to generate control signals.

One example of operation of the cardiac pacing system in this embodimentwill be explained below. By the stimulation timing determining means,control signals are generated according to a predetermined stimulationtiming and the atrial endocardium is stimulated electrically. Thisresults in excitation and contraction of the atrial myocardium, while atthe same time this stimulus is conducted to the atrioventricular nodethrough intra-atrial conduction pathway. Then, from the atrioventricularnode, the stimulus is conducted to the His bundle, the left and rightbundle branch, the Purkinje fiber and finally exciting the ventricularmyocardium, resulting in a normal heart beat.

Even in sick sinus syndrome, a spontaneous heart beat may occur. If theelectrocardiographic information detecting means detects spontaneousintracardiac P wave information within a given predetermined time fromthe prior heart beat, this spontaneous intracardiac P wave informationis output into the control unit, meanwhile the timing of stimulation togenerate control signals is changed by the stimulation timing changingmeans of the control unit, and atrial pacing is suppressed. In casespontaneous intracardiac P wave information is not detected within agiven time interval after the detection of prior intracardiac P waveinformation, the atrial myocardium will be stimulated electricallyaccording to the predetermined stimulation timing.

By placing the above-mentioned ultra miniature integrated cardiacpacemaker in the ventricular endocardium of the patient, it is possibleto stimulate the ventricular myocardium. By applying this pacemaker topatients who have normal sinus node function and only impairedatrioventricular conduction, it is possible to maintain the clinicallyrequired minimal number of ventricular contraction although there is nosynchrony between the atrium and ventricle.

Next, a distributed cardiac pacing system according to anotherembodiment will be explained while referring to the diagrams.

FIG. 7 is a schematic diagram illustrating an outline of the distributedcardiac pacing system according to this embodiment. The schematicdiagram shows one electrocardiographic information detecting device(200) in the atrial endocardium and one ultra miniature integratedcardiac pacemaker in accordance with this invention (131) in theventricular endocardium. FIG. 8 is a block diagram illustrating theoutline of the electrocardiographic information detecting device (200).

The distributed cardiac pacing system in this embodiment is indicatedfor patients who have normal sinus node function and whoseatrioventricular conduction is only impaired. In detail, theelectrocardiographic information detecting device (200) placed in theatrial endocardium detects electrocardiographic information including atleast spontaneous intracardiac P wave information. The detectedelectrocardiographic information including spontaneous intracardiac Pwave information is transmitted to the ultra miniature integratedcardiac pacemaker (131) placed in the ventricular endocardium. Uponreceiving the electrocardiographic information of the spontaneousintracardiac P wave information from the electrocardiographicinformation detecting device (200) and after a given lag(atrioventricular delay equivalent to the PQ interval in theelectrocardiogram), the ultra miniature integrated cardiac pacemaker(131) conducts ventricular pacing by electrically stimulating theventricular myocardium by the heart stimulating means.

Even in patients with impaired atrioventricular conduction, spontaneousventricular contraction may occur. In these patients, if ventricularcontraction occurs (in case of detection of spontaneous intracardiac QRScomplex information) within a given time (atrioventricular delay) afterthe detection of spontaneous intracardiac P wave information, thestimulation timing is changed and ventricular pacing is not conducted.

FIG. 8 is a block diagram illustrating the outline of theelectrocardiographic information detection device (200) placed in theatrial endocardium. The electrocardiographic information detectiondevice (200) is composed of an electrocardiographic informationdetecting means (5) that detects the electrocardiographic informationincluding at least intracardiac P wave information and outputs theelectrocardiographic data, a transmitting means that sendselectrocardiographic information (10), and a control unit (2).

In the electrocardiographic information detection device (200) shown inthe diagram, the electrocardiographic information detecting means (5) iscomposed of two electrocardiographic information recording electrodes(53) that detect electrocardiographic information, an amplifying unit(51) that amplifies the electrocardiographic information (51), and anA/D conversion unit (52) that converts the electrocardiographicinformation into digital information.

Moreover, in the electrocardiographic information detection device (200)shown in the diagram, the transmitting means (10) is composed of amodulating unit (11) that inputs and modulates the electrocardiographicinformation output from the control unit (2), and a transmitting unit(12) that sends the modulated electrocardiographic information byspecified carrier wave. The modulated electrocardiographic informationis sent to the ultra miniature integrated cardiac pacemaker (131) placedin the ventricular endocardium.

The ultra miniature integrated cardiac pacemaker (131) placed in theventricle is composed of a control unit that outputs control signals, aheart stimulating means that responds to the control signal andelectrically stimulates the ventricular myocardium, anelectrocardiographic information detecting means that detects theelectrocardiographic information including at least intracardiac QRScomplexes, and a receiving means that receives and demodulates theelectrocardiographic information sent from the electrocardiographicinformation detection device (200) placed in the atrium. It is designedsuch that the electrocardiographic information detected by theelectrocardiographic detecting means and the electrocardiographicinformation sent from elsewhere is input into the control unit.Therefore, in the distributed cardiac pacing system of this embodiment,the ultra miniature integrated cardiac pacemakers of the fourthembodiment are preferably used as the ultra miniature integrated cardiacpacemakers placed in the ventricular endocardium, but the ultraminiature integrated cardiac pacemakers of the first embodiment can alsobe used without a problem.

Furthermore, the control unit is equipped with a stimulation timingdetermining means that decides the timing of stimulation to generatecontrol signals, and a stimulation timing changing means that changesthe timing of stimulation to generate control signals.

One example of operation of the distributed cardiac pacing system inthis embodiment will be explained below. Usually, the ventricle is pacedby the generation of control signals at a stimulation timing determinedby the stimulation timing determining device [pacing after a given timeinterval (atrioventricular delay) from the detection of intracardiac Pwave information].

If spontaneous intracardiac QRS complex information is detected within agiven time interval (atrioventricular delay) after the detection ofintracardiac P wave information, the timing of stimulation to generatecontrol signals is changed by the stimulation timing changing means, andcontrol signals are not generated.

The ultra miniature integrated cardiac pacemaker (131) is preferablydesigned such that the ventricle is paced at regular intervals if nointracardiac P wave information is sent from the electrocardiographicinformation detection device (200) within a given time interval afterintracardiac QRS complex information is detected (due to spontaneousventricular contraction or due to stimulation by a cardiac pacemaker).This design will assure safety if sinus arrest or sinoatrial blockoccurs.

Next, the distributed cardiac pacing system in another embodiment willbe explained while referring to the diagram. FIG. 9 is a schematicdiagram illustrating a distributed cardiac pacing system according tothis embodiment. The diagram shows a first ultra miniature integratedcardiac pacemaker (101) placed in the atrial endocardium and a secondultra miniature integrated cardiac pacemaker (102) placed in theventricular endocardium.

The distributed cardiac pacing system in this embodiment may beindicated for patients with malfunction of the sinus node together withimpaired atrioventricular conduction. In other words, this pacemaker isindicated for patients with sick sinus syndrome with manifestations ofboth arrest of sinus function and atrioventricular block.

One example of operation of the distributed cardiac pacing system inthis embodiment will be explained. The first ultra miniature integratedcardiac pacemaker (101) placed in the atrial endocardium outputs controlsignals and paces the atrium by the heart stimulating means. Thiscontrol signal (and/or electrocardiographic information of atrium) ismodulated into carrier waves and transmitted to the second ultraminiature integrated cardiac pacemaker (102) placed in the ventricularendocardium. Upon receiving the control signals (and/orelectrocardiographic information of the atrium) from the first ultraminiature integrated cardiac pacemaker (101), the second ultra miniatureintegrated cardiac pacemaker (102) outputs control signals with a givendelay (atrioventricular delay equivalent to the PQ interval onelectrocardiogram) after the atrial pacing by the first ultra miniatureintegrated cardiac pacemaker (102), and electrically stimulates theventricular myocardium to conduct ventricular pacing. Furthermore, thiscontrol signal (and/or electrocardiographic information of theventricle) is modulated into a carrier wave and transmitted to the firstultra miniature integrated cardiac pacemaker (101). The first ultraminiature integrated cardiac pacemaker (101) suppresses detection ofintracardiac P wave for a given time interval after receiving thecontrol signal (and/or electrocardiographic information of theventricle) from the second ultra miniature integrated cardiac pacemaker(102). Thereafter, the first ultra miniature integrated cardiacpacemaker (101) outputs control signals at a stimulation timingaccording to a predetermined rate, and stimulates the atrium.

By repeating the above, it is possible to pace the heart and mimic thenatural physiological state.

Even patients with sick sinus syndrome with manifestations of botharrest of sinus function and atrioventricular block may generatespontaneous ventricular contraction or atrial contraction. Ifspontaneous intracardiac P wave information is detected within a giventime from the prior heart beat, then the atrial pacing is suppressed.Moreover, if spontaneous intracardiac QRS complex information isdetected within a given time interval (atrioventricular delay) after thedetection of intracardiac P wave information (spontaneous or due to thefirst ultra miniature integrated cardiac pacemaker), then ventricularpacing is suppressed.

The first ultra miniature integrated cardiac pacemaker (101) placed inthe atrial endocardium is equipped with a control unit that outputscontrol signals, a heart stimulating means that responds to the controlsignal and electrically stimulates the atrial myocardium, anelectrocardiographic information detecting means that detects theelectrocardiographic information including at least intracardiac P waveinformation, a transmitting means that modulates the control signal orelectrocardiographic information and sends the information to the secondultra miniature integrated cardiac pacemaker (102) placed in theventricle, and a receiving means that receives and demodulates thecontrol signal or electrocardiographic information sent from the secondultra miniature integrated cardiac pacemaker (102) placed in theventricle. The pacemaker is designed such that the control signal andelectrocardiographic information sent from the second ultra miniatureintegrated cardiac pacemaker (102) are input into the control unit.Therefore, in the distributed cardiac pacing system of this embodiment(101), the ultra miniature integrated cardiac pacemaker of the firstembodiment is preferably used as the first ultra miniature integratedcardiac pacemaker (101).

The second ultra miniature integrated cardiac pacemaker (102) isequipped with a control unit that outputs control signals, a heartstimulating means that responds to the control signal and electricallystimulates the ventricular myocardium, an electrocardiographicinformation detecting means that detects the electrocardiographicinformation including at least intracardiac QRS complex information, atransmitting means that modulates the control signal orelectrocardiographic information and sends the information to the firstultra miniature integrated cardiac pacemaker (101), and a receivingmeans that receives and demodulates the control signal orelectrocardiographic information sent by the first ultra miniatureintegrated cardiac pacemaker (101) placed in the atrium. The pacemakeris designed such that the control signal and electrocardiographicinformation sent from the first ultra miniature integrated cardiacpacemaker (101) are input into the control unit. Therefore, in thedistributed cardiac pacing system of this embodiment, the abovementionedultra miniature integrated cardiac pacemaker of the first embodiment ispreferably used as the second ultra miniature integrated cardiacpacemaker (102).

In the first ultra miniature integrated cardiac pacemaker (101), thecontrol unit is equipped with a stimulation timing determining meansthat decides the timing of stimulation to generate control signals, anda stimulation timing changing means that changes the timing ofstimulation to generate control signals.

Usually, the stimulation timing determining means decides the timing ofstimulation of control signal generation, and then generates controlsignals to conduct atrial pacing.

One example of operation of the first ultra miniature integrated cardiacpacemaker (101) will be explained. If the electrocardiographicinformation detecting means detects spontaneous intracardiac P wavewithin a given time from the prior heart beat, the timing of stimulationto generate control signals is changed, a control signal is notgenerated and atrial pacing is not conducted. If theelectrocardiographic information detecting means does not detectspontaneous intracardiac P wave information within a given time intervalfrom the last heart beat, then a control signal is generated and atrialpacing is conducted.

Moreover, in the control unit, if the control signal is generated orspontaneous intracardiac P wave information is detected, the informationis sent from the transmitting unit to the second ultra miniatureintegrated cardiac pacemaker (102).

In the second ultra miniature integrated cardiac pacemaker (102), thecontrol unit is equipped with a stimulation timing determining meansthat decides the timing of stimulation to generate control signals, anda stimulation timing changing means that changes the timing ofstimulation to generate control signals.

One example of operation of the second ultra miniature integratedcardiac pacemaker (102) will be explained. Usually, a control signal isgenerated at a timing predetermined by the timing determining means [thecontrol signal is generated at a given time interval (atrioventriculardelay) after the control signal or intracardiac P wave information issent from the first ultra miniature integrated cardiac pacemaker (101)].

If spontaneous intracardiac QRS complex information is detected within agiven time (atrioventricular delay), the timing of stimulation togenerate control signals is changed by the stimulation timing changingmeans and ventricular pacing is not conducted.

Moreover, in the control unit, if a control signal is generated orspontaneous intracardiac QRS wave information is detected, theinformation is sent from the transmitting unit to the first ultraminiature integrated cardiac pacemaker (101). The first ultra miniatureintegrated cardiac pacemaker (101) suppresses the detection ofintracardiac P wave information for a given time interval afterreceiving the control signal (or electrocardiographic information of theventricle) from the second ultra miniature integrated cardiac pacemaker(102). This design is essential to prevent the complication of so calledpacemaker tachycardia caused by the following mechanism: whenintracardiac QRS complex due to spontaneous ventricular contraction isconducted retrograde to the atrium, the first ultra miniature integratedcardiac pacemaker detects intracardiac P wave information, based onwhich the second ultra miniature integrated cardiac pacemakerelectrically stimulates the ventricle, resulting in repeated electricalstimulation of the ventricle.

Next, a distributed cardiac pacing system in another embodiment will beexplained while referring to the diagram. FIG. 10 is a schematic diagramillustrating the distributed cardiac pacing system in this embodiment.The diagram shows an electrocardiographic information detecting device(200) placed in the atrial endocardium and multiple (for example, atotal of 4 in FIG. 10) ultra miniature integrated cardiac pacemakers(102) placed in the ventricular endocardium.

The distributed cardiac pacing system in this embodiment may beindicated for patients with impaired synchrony of ventricular myocardialcontraction leading to lowered ventricular contractility, or patients atrisk for fatal arrhythmia.

One example of operation of this distributed cardiac pacing system willbe explained. The electrocardiographic information detecting device(200) placed in the atrial endocardium detects electrocardiographicinformation including at least intracardiac P wave information. Thedetected electrocardiographic information is sent to multiple ultraminiature integrated cardiac pacemakers (102) placed in the ventricularendocardium. Once electrocardiographic information is sent from theelectrocardiographic information detecting device (200), multiple ultraminiature integrated cardiac pacemakers (102) generate control signalsto stimulate the ventricular myocardium and pace the ventricle with adelay after atrial contraction in time lags that vary depending on theindividual ultra miniature integrated cardiac pacemakers (102). In otherwords, once electrocardiographic information is sent from theelectrocardiographic information detecting device (200), the multipleultra miniature integrated cardiac pacemakers (102) pace the ventricleafter predetermined times depending on the ventricular sites at whichthe individual ultra miniature integrated cardiac pacemakers (102) areplaced.

If spontaneous ventricular contraction occurs, that is, if spontaneousintracardiac QRS complex information is detected within a given timeinterval (atrioventricular delay) after the detection of intracardiac Pwave information, ventricular pacing is suppressed. However, even thoughspontaneous intracardiac QRS complex information is detected, if thespontaneous beat is not detected within given time intervals at othermultiple ultra miniature integrated cardiac pacemakers (102) placed inthe ventricular endocardium, the ventricular pacing at these sites willnot be suppressed. In order to realize this, spontaneous intracardiacQRS complex information recorded by a pacemaker (102) at any site of theventricle is transmitted to other ventricular pacemakers (102). Eachventricular pacemaker (102) mutually receives the signals sent fromother ventricular pacemakers (102).

The ultra miniature integrated cardiac pacemaker (102) placed in theventricular endocardium is equipped with a control unit that outputscontrol signals, a heart stimulating means that responds to controlsignals and electrically stimulates the ventricular myocardium, anelectrocardiographic information detecting means that detects theelectrocardiographic information including at least intracardiac QRScomplex information, a transmitting means that modulates the controlsignal or electrocardiographic information and sends the information toother ultra miniature cardiac pacemakers placed in the ventricle, and areceiving means that receives and demodulates control signals orelectrocardiographic information sent by the electrocardiographicinformation detecting device (200) placed in the atrium and other ultraminiature integrated cardiac pacemakers placed in the ventricle.Therefore, in this embodiment, the aforementioned ultra miniatureintegrated cardiac pacemakers of the first embodiment (100) arepreferably used as the ultra miniature integrated cardiac pacemakers(102).

In addition, the sites where the ultra miniature integrated cardiacpacemakers are to be placed and the number of the pacemakers will be setappropriately in accordance with the patient's symptoms.

The control unit of each ultra miniature integrated cardiac pacemaker(102) is equipped with a stimulation timing determining means thatdecides the timing of stimulation to generate control signals, and astimulation timing changing means that changes the timing of stimulationto generate control signals.

One example of operation of the ultra miniature integrated cardiacpacemaker will be explained. The stimulation timing determining meansgenerates a control signal at a predetermined stimulation timing[generates a control signal at a given time interval (atrioventriculardelay) after spontaneous intracardiac P wave information is transmittedfrom the electrocardiographic information detecting device (200)], andventricular pacing is conducted.

The stimulation timing is different for each of the ultra miniatureintegrated cardiac pacemakers; in other words, it differs depending onthe placement site of the pacemakers in the ventricular endocardium. Forexample, each ultra miniature integrated cardiac pacemaker (102) isstimulated with a time lag depending on when the site is stimulated inthe normal ventricular beat. But, the above-mentioned combination is notrestricted as long as it is a combination that maximally improves thecontractility of the heart.

This kind of synchronized cardiac contraction also reduces theelectrical instability of the ventricle, and is used to preventarrhythmia in patients with a risk of fatal arrhythmia, and also toprevent pacemaker-induced arrhythmia.

The intracardiac QRS complex information detected by the ultra miniatureintegrated cardiac pacemaker (102) is transmitted to other ultraminiature integrated cardiac pacemakers via the transmitting means. If acertain ventricular pacemaker detects spontaneous intracardiac QRScomplex within the predetermined time but this spontaneous beat is notdetected at other ventricular pacemakers within given times, theabove-mentioned design ensures that ventricular pacing also takes placein these sites.

In the distributed cardiac pacing system, it is possible to place anultra miniature integrated cardiac pacemaker (101), instead of theelectrocardiographic information detecting device (200), in the atrialendocardium just like the above-mentioned distributed cardiac pacingsystem in the previous embodiment. As described in the distributedcardiac pacing system in the previous embodiment (i.e., the thirdembodiment of the distributed cardiac pacing system), the ultraminiature integrated cardiac pacemaker placed in the atrial endocardiumis equipped with a stimulation timing determining means and stimulationtiming changing means, and therefore may be used in patients withlowered ventricular contractility accompanying sinus arrest andatrioventricular block, as well as in patients with a risk of fatalarrhythmia accompanying sinus arrest and atrioventricular block.

In the distributed cardiac pacing system of this revised embodiment, forthe design of the ultra miniature integrated cardiac pacemaker placed inthe atrial endocardium, one may adopt the design of the ultra miniatureintegrated cardiac pacemaker (101) placed in the atrial endocardium inthe above-mentioned distributed cardiac pacing system in accordance withthe previous embodiment (i.e., the third embodiment of the distributedcardiac pacing system). Furthermore, in the distributed cardiac pacingsystem in accordance with this revised embodiment for the design of theultra miniature integrated cardiac pacemaker placed in the ventricularendocardium, one may adopt the design of the ultra miniature integratedcardiac pacemaker (102) placed in the ventricular endocardium in theabove-mentioned distributed cardiac pacing system in this embodiment(i.e., the fourth embodiment of the distributed cardiac pacing system).

The ultra miniature integrated cardiac pacemaker in one embodimenttransmits control signals or electrocardiographic information to otherultra miniature integrated cardiac pacemakers and at the same timereceives control signals or electrocardiographic information from otherultra miniature integrated cardiac pacemakers; thus it is able to pacethe heart in synchrony with other ultra miniature integrated cardiacpacemakers.

The ultra miniature integrated cardiac pacemaker in another embodimentdoes not require lead wires to connect the pacemaker main body with thestimulation electrodes; thus it is able to pace the heart withoutimposing extra burden on the patient.

The ultra miniature integrated cardiac pacemaker in another embodimenttransmits control signals or electrocardiographic information to otherultra miniature integrated cardiac pacemakers; thus it is able to pacethe heart in synchrony with other ultra miniature integrated cardiacpacemakers.

The ultra miniature integrated cardiac pacemaker in yet anotherembodiment receives control signals or electrocardiographic informationfrom other ultra miniature integrated cardiac pacemakers; thus it isable to pace the heart in synchrony with other ultra miniatureintegrated cardiac pacemakers.

The distributed cardiac pacemaker system in another embodiment can beused for pacing in patients whose atrium has lost the ability to keeppace although the electrical activity in the atrium and the electricalactivity in the ventricle remain synchronized.

The distributed cardiac pacemaker system in still another embodiment canbe used in patients with normal sinus node function but in whomatrioventricular conduction is only impaired.

The distributed cardiac pacemaker system in another embodiment can beused in patients whose sinus node is not functioning normally andatrioventricular conduction is also impaired.

The distributed cardiac pacemaker system in yet another embodiment canbe used in patients who have lost synchrony of contraction among variousparts of the ventricle together with lowered ventricular contractility,or patients with arrhythmia.

The distributed cardiac pacemaker system in another embodiment can beused in patients with lowered ventricular contractility accompanyingsinus arrest and atrioventricular block, as well as patients with a riskof fatal arrhythmia accompanying sinus arrest and atrioventricularblock.

The present invention provides an ultra miniature integrated cardiacpacemaker and distributed cardiac pacing system which allow pacing ofthe heart without the need for the conventional lead wires that connectthe electrodes with the pacemaker main body, and allow implantation inthe heart by catheter manipulation only without incision of the chestwall to reduce burden on the patient.

Accordingly, it is to be understood that the embodiments of theinvention herein described are merely illustrative of the application ofthe principles of the invention. Reference herein to details of theillustrated embodiments is not intended to limit the scope of theclaims, which themselves recite those features regarded as essential tothe invention.

1. A first ultra miniature integrated cardiac pacemaker adapted to bepart of a distributed cardiac pacing system comprising at least onesecond ultra miniature integrated cardiac pacemaker, wherein the firstultra miniature integrated cardiac pacemaker is adapted to be implantedinto a heart of a patient, the first ultra miniature integrated cardiacpacemaker comprising: a) a control unit that outputs at least onecontrol signal; b) a heart stimulating means that responds to thecontrol signal and electrically stimulates heart tissue; c) anelectrocardiographic information detecting means that detects aplurality of electrocardiographic information and outputs theelectrocardiographic information to the control unit; d) a transmittingmeans to modulate the electrocardiographic information and controlsignal and to send the modulated electrocardiographic information andthe modulated control signal outside of the first ultra miniatureintegrated cardiac pacemaker via a plurality of carrier waves to atleast one of the second ultra miniature integrated cardiac pacemakersadapted to be implanted into the heart of the patient; e) a receivingmeans to demodulate information transmitted from at least one of thesecond ultra miniature integrated cardiac pacemakers adapted to beimplanted into the heart; and f) a power unit that supplies the drivingpower; wherein the first ultra miniature integrated cardiac pacemakerrequires no chest incision, and can be implanted into a heart byattaching the first ultra miniature integrated cardiac pacemaker to atip of a catheter and extracting the catheter after implantation;wherein the first ultra miniature integrated cardiac pacemaker isdesigned such that information sent from at least one of the secondultra miniature integrated cardiac pacemakers is input into the controlunit after the information is demodulated by the receiving means;wherein the control unit of the first ultra miniature integrated cardiacpacemaker outputs the control signal based on information selected fromthe group consisting of a) information sent from at least one of thesecond ultra miniature integrated cardiac pacemakers; b)electrocardiographic information; and c) a combination of a) and b);wherein the control unit of the first ultra miniature integrated cardiacpacemaker outputs the control signal based on the information sent fromat least one of the second ultra miniature integrated cardiac pacemakersto pace the heart and mimic a natural physiological state of the heart;wherein the control unit includes a stimulation timing determining meansthat determines the timing of stimulation to generate control signals,and a stimulation timing changing means that changes the timing ofstimulation to generate control signals; wherein the control unitchanges the stimulation timing when certain conditions are fulfilled;wherein the power unit is a biological fuel cell that extracts electronsfrom oxidative reactions of biological fuels; wherein the biologicalfuel cell is composed of an anode and a cathode; wherein the anodecomprises an anode electrode and an immobile layer formed on a surfaceof the anode electrode by immobilization of mediators and oxidativeenzymes for biological fuels, wherein said immobile layer preventsoxygen existing in a biological body from contacting said anodeelectrode; wherein the cathode comprises a cathode electrode and acoating material formed on a surface of the cathode electrode, whereinthe cathode electrode is composed of a catalyst to enhance a reactioninvolving reduction of oxygen, and wherein said coating material iscapable of preventing permeation of reactive substances other thanoxygen and allowing permeation of oxygen and hydrogen ions; wherein thebiological fuel cell uses an electrolyte solution selected from thegroup consisting of blood; body fluid; and blood and body fluid, andutilizes biological fuels and oxygen in the electrolyte solution withoutthe need for a container to contain the electrolyte solution or ametabolic product; and wherein said anode and said cathode are adaptedto contact the electrolyte solution.
 2. The ultra miniature integratedcardiac pacemaker of claim 1, wherein the first ultra miniatureintegrated cardiac pacemaker is adapted to be placed on an atrium or aventricle of the heart of the patient.
 3. A distributed cardiac pacingsystem comprising the ultra miniature integrated cardiac pacemaker ofclaim 1 and at least one second ultra miniature integrated cardiacpacemaker adapted to be placed on an atrium or a ventricle of the heartof the patient.
 4. A first ultra miniature integrated cardiac pacemakeradapted to be part of a distributed cardiac pacing system comprising atleast one second ultra miniature integrated cardiac pacemaker, whereinthe first ultra miniature integrated cardiac pacemaker is adapted to beimplanted into a heart of a patient, the first ultra miniatureintegrated cardiac pacemaker comprising: a) a control unit that outputsat least one control signal; b) a heart stimulating means that respondsto the control signal and electrically stimulates heart tissue; c) anelectrocardiographic information detecting means that detects aplurality of electrocardiographic information and outputs theelectrocardiographic information to the control unit; d) a transmittingmeans to modulate the electrocardiographic information and controlsignal and to send the modulated electrocardiographic information andthe modulated control signal via a plurality of carrier waves to atleast one of the second ultra miniature integrated cardiac pacemakersadapted to be implanted into the heart of the patient; e) a receivingmeans to demodulate information transmitted from at least one of thesecond ultra miniature integrated cardiac pacemakers; and f) a powerunit that supplies the driving power; wherein the first ultra miniatureintegrated cardiac pacemaker requires no chest incision, and can beimplanted into a heart by attaching the first ultra miniature integratedcardiac pacemaker to a tip of a catheter and extracting the catheterafter implantation; wherein the first ultra miniature integrated cardiacpacemaker is designed such that the information sent from at least oneof the second ultra miniature integrated cardiac pacemakers is inputinto the control unit after the information is demodulated by thereceiving means; wherein the control unit of the first ultra miniatureintegrated cardiac pacemaker outputs the control signal based on theinformation sent from at least one of the second ultra miniatureintegrated cardiac pacemakers adapted to be implanted into the heart topace the heart and mimic a natural physiological state of the heart;wherein the control unit includes a stimulation timing determining meansthat determines the timing of stimulation to generate control signals,and a stimulation timing changing means that changes the timing ofstimulation to generate control signals; wherein the control unitchanges the stimulation timing when certain conditions are fulfilled;wherein the power unit is a biological fuel cell that extracts electronsfrom oxidative reactions of biological fuels; wherein the biologicalfuel cell is composed of an anode and a cathode; wherein the anodecomprises an anode electrode and an immobile layer formed on a surfaceof the anode electrode by immobilization of mediators and oxidativeenzymes for biological fuels, wherein said immobile layer preventsoxygen existing in a biological body from contacting said anodeelectrode; wherein the cathode comprises a cathode electrode and acoating material formed on a surface of the cathode electrode, whereinthe cathode electrode is composed of a catalyst to enhance a reactioninvolving reduction of oxygen, and wherein said coating material iscapable of preventing permeation of reactive substances other thanoxygen and allowing permeation of oxygen and hydrogen ions; wherein thebiological fuel cell uses an electrolyte solution selected from thegroup consisting of blood; body fluid; and blood and body fluid, andutilizes biological fuels and oxygen in the electrolyte solution withoutthe need for a container to contain the electrolyte solution or ametabolic product; and wherein said anode and said cathode are adaptedto contact the electrolyte solution.
 5. The pacemaker of claim 4,wherein the control unit outputs the control signal based on additionalinformation comprising electrocardiographic information.
 6. The ultraminiature integrated cardiac pacemaker of claim 4, wherein the firstultra miniature integrated cardiac pacemaker is adapted to be placed onan atrium or a ventricle of the heart of the patient.
 7. A distributedcardiac pacing system comprising the ultra miniature integrated cardiacpacemaker of claim 4 and at least one second ultra miniature integratedcardiac pacemaker adapted to be placed on an atrium or a ventricle ofthe heart of the patient.